Functional Organotypic Cultures of Prostate Tissues: A Relevant Preclinical Model That Preserves Hypoxia Sensitivity and Calcium Signaling
| Autor: | Sandy, Figiel, Côme, Pasqualin, Fanny, Bery, Veronique, Maupoil, Christophe, Vandier, Marie, Potier-Cartereau, Isabelle, Domingo, Roseline, Guibon, Franck, Bruyere, Karine, Maheo, Gaelle, Fromont |
|---|---|
| Přispěvatelé: | Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Signalisation et Transports Ioniques Membranaires (STIM), Université de Poitiers-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), CCSD, Accord Elsevier, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours, Université de Poitiers-Université de Tours-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
[SDV.MHEP.AHA] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] Prostatic Neoplasms Zinc Finger E-box-Binding Homeobox 1 [SDV.CAN]Life Sciences [q-bio]/Cancer Middle Aged Prostate-Specific Antigen Models Biological [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology Cell Hypoxia Neoplasm Proteins Tissue Culture Techniques Transcriptional Regulator ERG [SDV.CAN] Life Sciences [q-bio]/Cancer Antigens Neoplasm Tumor Microenvironment [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] Humans Calcium Kallikreins Calcium Signaling Carbonic Anhydrase IX Aged |
| Zdroj: | American Journal of Pathology American Journal of Pathology, 2019, 189 (6), pp.1268-1275. ⟨10.1016/j.ajpath.2019.02.017⟩ American Journal of Pathology, American Society for Investigative Pathology, 2019, 189 (6), pp.1268-1275. ⟨10.1016/j.ajpath.2019.02.017⟩ |
| ISSN: | 0002-9440 1525-2191 |
| Popis: | International audience; In prostate cancer research, there is a lack of valuable preclinical models. Tumor cell heterogeneity and sensitivity to microenvironment signals, such as hypoxia or extracellular calcium concentration, are difficult to reproduce. Here, we developed and characterized an ex vivo tissue culture model preserving these properties. Prostate tissue slices from 26 patients were maintained ex vivo under optimized culture conditions. The expression of markers associated with proliferation, androgen-receptor signaling, and hypoxia was assessed by immunostaining. A macroscope was used to achieve real-time calcium fluorescence optical imaging. Tissue morphology was maintained successfully without necrosis for 5 days. Compared with native tumors and tissue cultured with androgens, androgen deprivation in the medium led to decreased expression of both androgen receptor and its target gene products, prostate specific antigen (PSA) and ETS-related gene (ERG). Ex vivo cultured slices also were sensitive to hypoxia because carbonic anhydrase IX and zinc finger E-box binding homeobox 1 (Zeb1) protein levels increased in 1% oxygen. Exposure of slices to supraphysiological extracellular Ca2+ concentration induced a robust and rapid Ca2+ entry, with a greater response in tumor compared with nontumor tissue. This ex vivo model reproduces the morphologic and functional characteristics of human prostate cancer, including sensitivity to androgen deprivation and induced response to hypoxia and extracellular Ca2+. It therefore could become an attractive tool for drug response prediction studies. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|